Spontaneously hypertensive rats (SHR), now at F33 generation, have been maintained as 8 substrains. Based on our observation of the greater incidence of stroke in two substrains, we made the successive selective breeding from them by our principles and succeeded in the establishment of stroke-prone SHR (1973). These SHR have maintained as high a spontaneous incidence of stroke as about 80% in males and about 60% in females, while some substrains, stroke-resistant SHR, have kept the low incidence of stroke around 5%. These SHR with different vulnerability to vascular lesions are obviously unique materials for the studies on hypertension sequelae (stroke, arteriosclerosis, myocardial lesions and nephrosclerosis). So, we propose the present project to achieve the following aims: (a) Genetic pathogenesis and modifying environmental factors of stroke are studied on the items below to establish the methods for prescience and prophylaxis of stroke; (1) The further continuation of selective breeding of stroke-prone SHR to concentrate the genetic disposition of stroke. (2) Biochemical, physical, physiological and morphological characteristics of blood vessels and neural or humoral factors or symptomatology and behavioral features of stroke-prone SHR. (3) Genetic analysis of stroke by the cross breeding between stroke-prone and -resistant SHR or Wistar rats. (4) Blood pressure control by antihypertensive agents at various ages to prevent stroke. (5) An attempt for the selection of SHR with cerebral lesions in basal ganglia. (b) Arteriosclerotic and myocardial lesions are studied in stroke-prone and other SHR to elucidate the genetic disposition and environmental influences such as high fat-cholesterol diet with or without salt. (c) Nephrosclerosis is studied in various SHR substrains under different dietary conditions such as high protein- salt diet to evaluate the genetic and environmental factors in the organ selectivity of hypertension sequelae.